A drug used to treat asthma and allergies can bind to and block a crucial protein produced by the virus SARS-CoV-2, and reduce viral replication in human immune cells, according to a new study by researchers at the Indian Institute of Science (IISc).
Approved by the US Food and Drug Administration (FDA), the drug, called montelukast, has been around for more than 20 years and is usually prescribed to reduce inflammation caused by conditions like asthma, hay fever and hives, said an IISc release.
In the study published in eLife, the researchers show that the drug binds strongly to one end (‘C-terminal’) of a SARS-CoV-2 protein called Nsp1, which is one of the first viral proteins unleashed inside the human cells. This protein can bind to ribosomes – the protein-making machinery – inside our immune cells and shut down the synthesis of vital proteins required by the immune system, thereby weakening it. Targeting Nsp1 could therefore reduce the damage inflicted by the virus, the release explained.
“The mutation rate in this protein, especially the C-terminal region, is very low compared to the rest of the viral proteins,” explained Tanweer Hussain, Assistant Professor in the Department of Molecular Reproduction, Development and Genetics (MRDG), IISc, and senior author of the study.
Computational modelling
Prof. Hussain and his team first used computational modelling to screen more than 1,600 FDA-approved drugs in order to find the ones that bound strongly to Nsp1. From these, they were able to shortlist a dozen drugs including montelukast and saquinavir, an anti-HIV drug. Working with the group of Sandeep Eswarappa, Associate Professor in the Department of Biochemistry, Prof. Hussain’s team then cultured human cells in the lab that specifically produced Nsp1, treated them with montelukast and saquinavir separately, and found that only montelukast was able to rescue the inhibition of protein synthesis by Nsp1, explained the release.
Prof. Hussain’s lab then tested the effect of the drug on live viruses, in the Bio-Safety Level 3 (BSL-3) facility at the Centre for Infectious Disease Research (CIDR), IISc, in collaboration with Shashank Tripathi, Assistant Professor at CIDR, and his team. They found that the drug was able to reduce viral numbers in infected cells in the culture.
Reduced hospitalisation
“Clinicians have tried using the drug… and there are reports that said that montelukast reduced hospitalisation in COVID-19 patients,” Prof. Hussain said in the release. His team plans to work with chemists to see if they can modify the structure of the drug to make it more potent against SARS-CoV-2.
